Variant 14-57210005-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006544.4(EXOC5):c.1670A>G(p.Lys557Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EXOC5
NM_006544.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

EXOC5 (HGNC:10696): (exocyst complex component 5) The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. The complex is also essential for the biogenesis of epithelial cell surface polarity. [provided by RefSeq, Jul 2008]

EXOC5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EXOC5	NM_006544.4 linkuse as main transcript	c.1670A>G	p.Lys557Arg	missense_variant	16/18	ENST00000621441.5
EXOC5	XM_005267272.4 linkuse as main transcript	c.1784A>G	p.Lys595Arg	missense_variant	16/18
EXOC5	XM_047430882.1 linkuse as main transcript	c.1505A>G	p.Lys502Arg	missense_variant	16/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EXOC5	ENST00000621441.5 linkuse as main transcript	c.1670A>G	p.Lys557Arg	missense_variant	16/18	1	NM_006544.4	P1
EXOC5	ENST00000554011.5 linkuse as main transcript	n.1389A>G		non_coding_transcript_exon_variant	6/8	1
EXOC5	ENST00000340918.11 linkuse as main transcript	c.1475A>G	p.Lys492Arg	missense_variant	15/17	2
EXOC5	ENST00000555148.5 linkuse as main transcript	c.*1504A>G		3_prime_UTR_variant, NMD_transcript_variant	16/18	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446998

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719760

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.1670A>G (p.K557R) alteration is located in exon 16 (coding exon 16) of the EXOC5 gene. This alteration results from a A to G substitution at nucleotide position 1670, causing the lysine (K) at amino acid position 557 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Benign

-0.16

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.0

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

Sift4G

Benign

0.10

T;T;T

Polyphen

0.92

P;.;D

Vest4

0.71

MutPred

0.44

Loss of methylation at K557 (P = 0.0159);.;.;

MVP

0.51

MPC

0.96

ClinPred

0.98

GERP RS

5.0

Varity_R

0.58

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over